DESCRIPTION (Taken from application) Exposure to arsenic has been associated with the induction of cancer in humans. It is widely accepted that arsenic can cause non-melanoma skin cancers (in particular, squamous-cell carcinoma). In addition, arsenic may be an important cause of bladder, lung, lung, and other internal cancers. We propose to study biomarkers of exposure, skin lesions, skin and bladder cancer, and heritable susceptibility in two populations: one in Taiwan, where remediation efforts have resulted in a reduction in arsenic exposure to ranges of one to three-hold in most US communities; and a second population in Bangladesh, an area recently described with extremely high exposures from drinking-water contamination. We propose a population-based approach, incorporating markers of exposure (drinking-water arsenic, toenail arsenic), susceptibility (genetic polymorphisms in metabolizing genes), and outcome (squamous-cell carcinoma of the skin, bladder, cancer, non-malignant skin lesions) in order to test several hypotheses important to advancing our understanding of the human-health consequence of arsenic exposure. We will conduct a repeat-measures study, designed to evaluate biologic markers including toenail concentrations, methylated arsenic compounds in the urine, and genetic traits. We will also conduct two case-control studies of skin and bladder cancer: one an extension of our ongoing work in Taiwan and the other in Bangladesh. These studies are designed to fill important research gaps in our understanding of arsenic and human health.